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Una Patologia Polidistrettuale:l’Aterotrombosi
Plinio Fabiani
3 ottobre 2009
Ospedale San Giovanni di DioFirenze
What is Atherothrombosis?
• Atherothrombosis is characterized by a sudden (unpredictable) atherosclerotic plaque disruption (rupture or erosion) leading to platelet activation and thrombus formation
• Atherothrombosis is the underlying condition that results in events leading to myocardial infarction, ischemic stroke, and vascular death
Plaque rupture1 Plaque erosion2
1. Falk E et al. Circulation 1995; 92: 657–71. 2. Arbustini E et al. Heart 1999; 82: 269–72.
La due fasi dell’atero-trombosi
Infarto Miocardico Acuto
Atherothrombosis: A Generalized and Progressive Process
Unstable angina
MI Ischemic stroke/TIACritical leg ischemiaCardiovasculardeath
ACS
Atherosclerosis
Adapted from Stary HC et al. Circulation. 1995; 92: 1355–74, and Fuster V et al. Vasc Med. 1998; 3: 231–9.
Stable angina Intermittent claudication
Atherothrombosis
Major Clinical Manifestations of Atherothrombosis
Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6.
Transient ischemic attack
Angina:• Stable• Unstable
Ischemicstroke
Myocardial infarction
Peripheral arterialdisease:• Intermittent claudication• Rest Pain• Gangrene• Necrosis
Plaquerupture
Platelet activation and aggregation
Non-occlusivethrombus
Acute syndrome:• coronary• cerebrovascular• peripheral
Occlusivethrombus
Healing andresolution
Plaque growth
The Development of Atherothrombosis – a Generalized and Progressive Process
Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6.
Atherothrombosis and Microcirculation
Adapted from: Topol EJ, Yadav JS. Circulation 2000; 101: 570–80, and Falk E et al. Circulation 1995; 92: 657–71.
Plaquerupture
Microvascular obstruction
Embolization
Atherothrombosis* is aLeading Cause of Death Worldwide†1
1. The World Health Report 2002. Geneva: WHO; 2002.
Mortality (%)
*Cardiovascular disease, ischemic heart disease and cerebrovascular disease†Worldwide defined as Member States by WHO Region (African, Americas, Eastern Mediterranean, European, South-East Asia and Western Pacific)
Identifying Those at Risk of Atherothrombosis1,2
1. Yusuf S et al. Circulation 2001; 104: 2746–53. 2. Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6.
Lifestyle• Smoking• Diet• Lack of exercise
Genetic• Genetic traits• Gender• Age
Generaliseddisorders• Obesity• Diabetes
Systemicconditions• History of vascular
events• Hypertension• Hyperlipidemia• Hypercoagulable
states• Homocystinemia
Local factors: • Elevated prothrombotic factors: fibrinogen, CRP, PAI-1• Blood flow patterns, vessel diameter, arterial wall structure
Atherothrombosis manifestations
(myocardial infarction, stroke, vascular death)
Il fumo uccide!
Atherothrombosis is a Systemic Disease: Increased Risk of Stroke in Patients After a
Myocardial Infarction1
1. Lichtman JH et al. Circulation 2002; 105: 1082–7.
0.93
1.43
2.08
2.72
3.58
4.17
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
0 1 2 3 4 5 or more
Six
mon
th s
trok
e ad
mis
sion
rat
e
Number of risk factors
Calcificazioni coronariche
L’aterosclerosi coronarica è il più comune fattore predisponenete per l’aterostrombosi
Atherothrombosis is a Systemic Disease: Long-Term Risk Increase for Stroke As a
Function of Coronary Calcification1
1. Vliegenthart R. Stroke 2002; 33: 462–5.
1.0
x 3.3
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
0–100 101–500 > 500
Coronary calcium score
Ris
k in
crea
se
1. O’Leary DH. N Engl J Med 1999; 340: 14–22.
1.0
x 3.61
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
1 2 3 4 5
Quintiles of carotid artery media thickness
Ris
k in
crea
seAtherothrombosis is a Systemic Disease:
Long-term Risk Increase for Myocardial Infarction as a Function of Carotid Intima Media Thickness1
Indice di Winsor (braccio/caviglia)
1. Dormandy JA, Creager MA. Cerebrovasc Dis 1999; 9(suppl 1): 14.
Atherothrombosis is a Systemic Disease: Increase for Myocardial Infarction and Stroke as
a Function of ABI Measurement1
x 2.2
1.0
1.5
2.0
2.5
1.0 0.8 0.6 0.4 0.2
Ankle-brachial index (ABI) index
Ris
k in
crea
se
Causes of Death During Different Time Intervals after First-Ever Stroke1
1. Hankey GJ. Stroke 2000; 31: 2080–6.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
< 30 days 30d–6m 6m–1yr 1–3yr 3–5yr
Time
Pro
po
rtio
n o
f d
eath
s (%
)
Unknown
Non-vascular
Cardiovascular
Recurrent stroke
Related to first stroke
Manifestations of Atherothrombosis are Commonly Found in More than One Arterial Bed in an Individual Patient*1
1. Coccheri S. Eur Heart J 1998; 19(suppl): P1268.
Coronary disease
Cerebrovascular disease
Peripheral arterial disease
24.7%
3.8% 11.8%
29.9%
3.3%
7.4%
19.2%
*Data from CAPRIE study (n=19,185)
Conclusioni
• L’Aterotrombosi è caratterizzata da un’improvvisa rottura di placca che determina attivazione piastrinica e formazione del trombo1
• L’aterotrombosi rappresenta il legame patologico comune a tutte le maggiori manifestazioni cliniche delle malattie vascolari: infarto del miocardio, ictus ischemico ed ateriopatia obliterante periferica2
• Pazienti con manifestazioni cliniche di aterotrombosi in un letto vascolare non sono solo a rischio di un evento ricorrente nella stessa distribuzione arteriosa, ma corrono il rischio di eventi ischemici anche in altri letti vascolari3
• L’Aterotrombosi è la maggiore causa di mortalità nel mondo intero4
1. Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 1–6. 2. Nenci GG. Eur Heart J 1999; 1(suppl A): A27–A30. 3. Lichtman JH et al. Circulation 2002; 105: 1082–7. 4. The World Health Report 2002.Geneva: WHO; 2002.